US11390632B2ActiveUtilityA1
Process for the preparation of 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo [1,2-B]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one derivatives
Est. expirySep 22, 2037(~11.2 yrs left)· nominal 20-yr term from priority
Inventors:Jean-Michel AdamSerena Maria FantasiaDaniel FishlockFabienne Hoffmann-EmeryGerard MoineChristophe PflegerChristian Moessner
C07D 487/04C07D 471/04C07D 401/04B01J 23/755B01J 23/44A61K 31/519A61K 31/496C07D 519/00
90
PatentIndex Score
3
Cited by
10
References
26
Claims
Abstract
The present invention relates to a process for the preparation of 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one derivatives useful as pharmaceutically active compounds.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1. A process for the preparation of a compound of formula (II)
which comprises reacting a compound of formula (III)
with a compound of formula (III′), (III a ′) or (III b ′)
in the presence of a palladium catalyst or nickel catalyst to form the compound of formula (II), wherein X is selected from an alkyl, aryl sulfonate, fluorinated alkyl, fluorinated aryl sulfonate and halide.
2. The process of claim 1 , wherein the compound of formula (III) is reacted with the compound of formula (III′), (III a ′) or (III b ′) in presence of a palladium catalyst.
3. The process of claim 1 , wherein X is selected from the group consisting of pTolSO 3— , CH 3 SO 3— , phenyl-SO 3— , CF 3 SO 3— , nonaflate, Cl, Br, and I.
4. The process of claim 1 , wherein said process is carried out in the presence of a base.
5. The process of claim 4 , wherein the base is selected from the group consisting of Na 2 CO 3 , K 2 CO 3 , Cs 2 CO 3 , KOAc and KOtBu.
6. The process of claim 5 , wherein the base is K 2 CO 3 .
7. The process of claim 4 , wherein said process is carried out in the presence of a palladium catalyst and base.
8. The process of claim 1 , wherein the compound of formula (III) is reacted with the compound of formula (III′).
9. The process of claim 8 , wherein said process further comprises
reacting a compound having formula
with bis(pinacolato)diboron to obtain the compound of formula (III′):
10. The process of claim 1 , wherein said process further comprises
reacting a compound of formula (IV)
with
tosyl chloride when X is pTol—SO 3— ,
methanesulfonyl chloride when X is CH 3 SO 3— ,
triflyl chloride when X is CF 3 SO 3— or
phenylsulfonylchloride when X is phenyl—SO 3— ,
in the presence of a base; or with
POCl 3 when X is Cl,
POBr 3 when X is Br, or
Ph 3 PI 2 or POCl 3 followed by NaI or CuI, when X is I
for the preparation of the compound of formula (III)
11. The process of claim 10 , wherein the base is an organic base or basic alkali metal salts.
12. The process of claim 11 , wherein the base is nitrogen-containing heterocycle, tertiary amine or basic alkali metal salts.
13. The process of claim 12 , wherein the base is a tertiary amine.
14. The process of claim 10 , wherein said process further comprises
reacting a compound of formula (V)
with di-tert-butyl malonate for the preparation of the compound of formula (IV)
15. The process of claim 14 , wherein said process is carried out in the presence of xylene, dichlorobenzene, toluene or anisole.
16. The process according to claim 15 , wherein said process is carried out in the presence of anisole.
17. The process of claim 14 , said process further comprising reducing a compound of formula (VI)
to provide the compound of formula (V)
18. The process of claim 17 , wherein reducing a compound of formula (VI) comprises reacting said compound with a transition metal hydrogenation catalyst to obtain the compound of formula (V).
19. The process according to claim 18 , wherein the transition metal hydrogenation catalyst is selected from the group consisting of a Raney catalyst, Pd/C, Pd(OH) 2 /C, Au/TiO 2 , Rh/C, Ru/Al 2 O 3 , Ir/CaCO 3 , Pt-V/C, Pt/C and combinations thereof.
20. The process according to claim 19 , wherein the transition metal hydrogenation catalyst is Pt-V/C.
21. The process according to claim 20 , wherein the transition metal hydrogenation catalyst is Pt 1% and V 2% on activated carbon.
22. The process of claim 17 , said process further comprising
reacting a compound of formula (VII)
with a compound of formula (VIII)
or a salt thereof for the preparation of the compound of formula (VI)
23. The process of claim 22 , wherein the salt is an oxalate salt.
24. A process for the preparation of a compound of formula (I)
said process comprising
preparing a compound of formula (II) comprising
reacting a compound of formula (III)
with a compound of formula (III′), (III a ′) or (III b ′)
in the presence of a palladium catalyst or nickel catalyst to form the compound of formula (II), wherein X is selected from an alkyl, aryl sulfonate, fluorinated alkyl, fluorinated aryl sulfonate and halide; and
reacting the compound of formula (II)
with a strong acid for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt thereof.
25. The process of claim 24 , wherein the strong acid is HCl.
26. The process of claim 25 , wherein the HCl is made in situ with 1-propanol and acetyl chloride.Cited by (0)
No later patents cite this yet.
References (0)
No backward citations on record.